The general objective is to ascertain whether neuromelanin is a factor in the pathogenesis of chlorpromazine (CPZ) induced tardive dyskinesia. It is known that CPZ produces pathology in skin and eye by reacting with their melanins. There is reason to believe that CPZ interaction with catecholamine-derived brain melanin is a factor in tardive dyskinesia. Two interrelated and immediate objectives are 1) to determine if protracted clinical administration of CPZ produces detectable histochemical changes in the neuromelanin of brains of psychiatric patients with and without tardive dyskinesia and, 2) to determine in vivo, whether the neuromelanin pigment in the brain stem of dog possesses the capacity to bind CPZ. Human brains to be studied are presently in storage at the applicant's dept. at the N.Y.S. Psychiatric Inst. Light microscopic tinctorial histochemistry and microfluorometry will be used to compare melanin, lipoproteinlike and soluble lipid components of neuromelanin of 3 types of patients; those treated with CPZ who developed tardive dyskinesia, those similarly treated with dyskinesia, and nonpsychiatric patients not given CPZ. The tinctorial methods will include the cupric and ferrous ion uptake methods for the melanin component, the acid fast, alcian blue, aldehyde fuchsin, naphthoic acid hydrazide, Schiff and Sudan black B reactions, each after oxidation to demonstrate carboxyl, aldehyde and sulfonic acid components of lipoproteinlike component, and the Holczinger, oil red O and Sudan III and IV methods to demonstrate the oxidized, soluble lipid component. Microfluorometry will be used to quantify the fluorescence of the combined soluble lipid-lipoproteinlike components of bleached neuromelanin. Aging dogs will be injected with 35S-CPZ in acute experiments. The aging dog is suited for this purpose as it is available, inexpensive, and has adequate amounts of neuromelanin in its hypothalamus, substantia nigra and locus ceruleus. Dry-mounting, thaw-mounting and paraffin light microscopic autoradiographic methods will serve to localize 35S-CPZ in the radiolabelled brains. Autoradiographs will also be made of lipofuscin-containing regions.